CN107629095B

CN107629095B - Hafnium trifluoromethanesulfonate-catalyzed peracetyl sugar terminal selective deprotection method

Info

Publication number: CN107629095B
Application number: CN201710903342.8A
Authority: CN
Inventors: 孙麒; 王蕊; 龚珊珊; 陈继宗; 孔瑞; 郑修安
Original assignee: Jiangxi Science and Technology Normal University
Current assignee: Jiangxi Science and Technology Normal University
Priority date: 2017-09-29
Filing date: 2017-09-29
Publication date: 2020-07-07
Anticipated expiration: 2037-09-29
Also published as: CN107629095A

Abstract

The invention relates to a selective deprotection method of a peracetyl sugar end position, which takes hafnium trifluoromethanesulfonate as a catalytic reagent, respectively takes peracetylated monosaccharide, disaccharide and trisaccharide as substrates, and acetonitrile containing a proper amount of water as a solvent, and can selectively and efficiently remove the acetyl at the 1-O position of the substrate under the condition of proper heating. The hafnium trifluoromethanesulfonate used in the invention has high catalytic activity and small dosage (the optimal catalytic effect can be achieved only by 2 mol%), and is generally suitable for various fully acetylated monosaccharides (D-type, L-type, pyran type and furan type), disaccharides and trisaccharide substrates (the separation yield can reach 82-95%). The method for catalyzing the hafnium trifluoromethanesulfonate has the advantages of mild reaction conditions (only 60 ℃ is needed for heating), no need of inert gas protection for a reaction system, and simple post-treatment and purification methods.

Description

Hafnium trifluoromethanesulfonate-catalyzed peracetyl sugar terminal selective deprotection method

Technical Field

The invention belongs to the technical field of chemical preparation of organic compounds, and relates to a method and a process for selective deprotection of a holoacetyl sugar terminal position catalyzed by hafnium trifluoromethanesulfonate.

Background

The regioselective deacetylation of the terminal of the peracetyl protected sugar raw material has important significance in the field of sugar chemical synthesis. In the oligosaccharide synthesis, the peracetylated half aldoses, namely products after selective deprotection of 1-O site of peracetylated sugar, can be further converted into glycosyl activated glycosyl fragments such as glycosyl trichloroacetimide, halogenated sugar, glycosyl phosphate and the like for construction of glycosidic bonds. In addition, the peracetylated hemiacetal saccharide is also an important synthetic structural unit for synthesizing various glycosyl conjugates with biological activity.

At present, there are two main types of selective deprotection methods for terminal positions of peracetyl sugars reported in the literature. One is the removal of terminal acetyl groups by transamidation using various nitrogen-containing nucleophilic (ammonia/amine) reagents. The main problems with this type of process are that it is usually necessary to use a large excess of ammonia/amine and that many reagents are toxic. Another method is to remove acetyl groups at the sugar residue end by alcoholysis or hydrolysis using protonic or Lewis acid reagents. At present, the metal Lewis acid catalysts reported in the literature only comprise a few of tributyl tin alkoxide, copper acetate, ferric trichloride, mercuric oxide/mercuric chloride, neodymium trifluoromethanesulfonate, zinc acetate and the like, and the removal yield of terminal acetyl is generally only about 70-80%, and some are even lower. Wherein only neodymium trifluoromethanesulfonate and zinc acetate are used in catalytic amounts (5-10% equivalent), and the other catalysts are used in equivalent amounts or even in excess. In addition, because neodymium trifluoromethanesulfonate and zinc acetate reaction system use methanol as a solvent, acetyl-based polydextrose byproducts are easily generated or glycosylation at glycosyl terminal sites is easily caused in practical application. Therefore, the efficient, universal and highly regioselective metal Lewis acid catalyst is found for the selective removal and protection of the terminal position of the peracetylated hemiacetal sugar, and has great practical application value for preparing the peracetylated hemiacetal sugar and the whole sugar chemical synthesis.

Disclosure of Invention

The invention aims to find a high-efficiency, universal and high-regioselectivity metal Lewis catalyst for the selective deacetylation reaction of the terminal position of the holoacetyl sugar, establish an optimized reaction system and obtain corresponding reaction conditions and processes.

The reaction route of the invention is as follows:

the invention relates to a selective deprotection method of a peracetyl sugar end position, which takes hafnium trifluoromethanesulfonate as a catalytic reagent, respectively takes peracetylated monosaccharide, disaccharide and trisaccharide as substrates, and acetonitrile containing a proper amount of water as a solvent, and can selectively and efficiently remove the acetyl at the 1-O position of the substrate under the condition of proper heating. The crude product was purified by conventional silica gel column chromatography to give 11 peracetyl hemiacetal sugar products (1-11) in high yield.

The chemical formula of the 11 peracetyl hemiacetal sugar products (1-11) is as follows:

in the present process, in order to optimize the reaction rate, selectivity and yield, the amount of the hafnium triflate catalyst used should be strictly controlled to 2 mol% (i.e. 0.02 times equivalent), the ideal reaction solvent requires acetonitrile with a water content of 0.3% (volume ratio) as solvent, and the ideal concentration of the substrate in the reaction solution is 0.15M (over-concentration or over-dilution affects the reaction rate and product yield). The reaction temperature must be strictly controlled at 60 deg.C (otherwise the reaction rate would be reduced or side reactions would be initiated to reduce the product yield). The reaction system is not required to be protected by inert gas, and the system is opened. The reaction time of the peracetylated monosaccharide is 6 hours, and the reaction time of the peracetylated disaccharide and the trisaccharide is slightly longer, and needs 8 hours. The post-treatment in the method only needs to concentrate the reaction system and directly carry out the conventional silica gel column chromatography.

Compared with the methods reported in the prior literature, the hafnium trifluoromethanesulfonate used in the invention has high catalytic activity and small dosage (only 2 mol% is needed to achieve the optimal catalytic effect), and is generally suitable for various fully acetylated monosaccharides (D-type, L-type, pyran type and furan type), disaccharides and trisaccharide substrates (the separation yield can reach 82-95%). The method for catalyzing the hafnium trifluoromethanesulfonate has the advantages of mild reaction conditions (only 60 ℃ is needed for heating), no need of inert gas protection for a reaction system, and simple post-treatment and purification methods.

Detailed Description

Example 1:

synthesis of 2,3, 4-triacetyl-L-rhamnopyranose (1): 1,2,3, 4-tetraacetyl-L-rhamnopyranose (2.0g, 6.0mmol) and hafnium triflate (93mg, 0.12mmol) were dissolved in acetonitrile (40mL, [ substrate ] ═ 0.15M) containing 0.3% by volume of water, and the reaction was stirred at 60 ℃ for 6 hours. The reaction solution was concentrated to give a crude product, which was subjected to silica gel column chromatography (petroleum ether/ethyl acetate 2: 1) to give 1.61g of 2,3, 4-triacetyl-L-rhamnopyranose (1) in 92% yield.

Example 2:

synthesis of 2,3,4, 6-tetraacetyl-D-glucopyranose (2): 1,2,3,4, 6-pentaacetyl-D-glucopyranose (2.0g, 5.1mmol) and hafnium triflate (79mg, 0.10mmol) were dissolved in acetonitrile (34mL, [ substrate ] ═ 0.15M) having a water content of 0.3% by volume, and the reaction was stirred at 60 ℃ for 6 hours. The reaction solution was concentrated to give a crude product, which was subjected to silica gel column chromatography (petroleum ether/ethyl acetate: 2: 1) to give 1.61g of 2,3,4, 6-tetraacetyl-D-glucopyranose (2) in 90% yield.

Example 3:

synthesis of 2,3, 4-triacetyl-D-xylopyranose (4): 1,2,3, 4-tetraacetyl-D-xylopyranose (2.0g, 6.3mmol) and hafnium triflate (98mg, 0.13mmol) were dissolved in acetonitrile (42mL, [ substrate ] ═ 0.15M) containing 0.3% by volume of water, and the reaction was stirred at 60 ℃ for 6 hours. The reaction solution was concentrated to give a crude product, which was subjected to silica gel column chromatography (petroleum ether/ethyl acetate ═ 2: 1) to give 1.62g of 2,3, 4-triacetyl-D-xylopyranose (4) in 93% yield.

Example 4:

synthesis of 2,3, 5-triacetyl-D-ribofuranose (7): 1,2,3, 5-tetraacetyl-D-ribofuranose (2.0g, 6.3mmol) and hafnium triflate (98mg, 0.13mmol) were dissolved in acetonitrile (42mL, [ substrate ] ═ 0.15M) containing 0.3% by volume of water, and the reaction was stirred at 60 ℃ for 6 hours. The reaction solution was concentrated to give a crude product, which was subjected to silica gel column chromatography (petroleum ether/ethyl acetate 2: 1) to give 1.63g of 2,3, 5-triacetyl-D-ribofuranose (7) in 94% yield.

Example 5:

synthesis of 4- (2,3,4, 6-tetraacetyl- α -D-glucopyranosyl) -2,3, 6-triacetyl-D-glucopyranose (9) The reaction was carried out by dissolving peracetylmaltobiose (4.0g, 5.9mmol) and hafnium triflate (91mg, 0.12mmol) in acetonitrile (39mL, [ substrate ] ═ 0.15M) having a water content of 0.3% by volume, reacting the resulting solution with heating at 60 ℃ under stirring for 8 hours, concentrating the reaction solution to give a crude product, and subjecting the crude product to silica gel column chromatography (petroleum ether/ethyl acetate ═ 2: 1) to give 3.19g of 4- (2,3,4, 6-tetraacetyl- α -D-glucopyranosyl) -2,3, 6-triacetyl-D-glucopyranosyl (9) in an 85% yield.

Example 6:

synthesis of 4- (4- (2,3,4, 6-tetraacetyl- α -D-glucopyranosyl) -2,3, 6-triacetyl- α -D-glucopyranosyl) -2,3, 6-triacetyl-D-glucopyranose (11) Peracetyl-protected maltotriose (5.0g, 5.2mmol) and hafnium triflate (81mg, 0.1mmol) were dissolved in acetonitrile (35mL, [ substrate ] ═ 0.15M) having a water content of 0.3% by volume, and the reaction mixture was heated and stirred at 60 ℃ for 8 hours to give a crude product, which was subjected to silica gel column chromatography (petroleum ether/ethyl acetate ═ 2: 1) to give 4- (4- (2,3,4, 6-tetraacetyl- α -D-glucopyranosyl) -2,3, 6-triacetyl- α -D-glucopyranosyl) -2,3, 6-triacetyl-D-glucopyranose (11) in 3.92g, 82% yield.

Claims

1. The selective deprotection method for the terminal position of the holoacetyl sugar catalyzed by hafnium trifluoromethanesulfonate is characterized in that: hafnium trifluoromethanesulfonate is used as a catalytic reagent, peracetylated monosaccharide, disaccharide and trisaccharide are used as substrates, water-containing acetonitrile is used as a solvent, the 1-O-position acetyl of the substrate is selectively and efficiently removed under the heating condition, and the crude product is subjected to conventional silica gel column chromatography purification to obtain a peracetylated hemiacetal sugar product with high yield;

wherein, the dosage of the hafnium triflate catalytic reagent is 2 mol%, the reaction solvent is acetonitrile with the water content volume ratio of 0.3%, the concentration of the substrate in the reaction solution is 0.15M, the reaction temperature is 60 ℃, the reaction time of the peracetylated monosaccharide is 6 hours, and the reaction time of the peracetylated disaccharide and the trisaccharide is 8 hours.